Functional diversity of GABA_A receptor ligand‐gated chloride channels in rat synaptoneurosomes

Abstract

Experiments were performed to examine neurochemically the functional diversity of GABAA receptors as measured by muscimol-, 5 alpha-pregnane-3 alpha,21-diol-20-one (THDOC)-, and pentobarbital-stimulated 36Cl- uptake, and region-specific changes in muscimol-, THDOC- and THDOC-induced potentiation of muscimol-stimulated 36Cl- uptake in rats treated acutely or subacutely with a subconvulsive dose of bicuculline. The data for stimulation of 36Cl- uptake by muscimol showed a single binding site interaction in the cerebral cortex, hippocampus and cerebellum. The concentration-response curves for muscimol in the cerebral cortex and hippocampus were steep and indicated an increase of approximately 130% at the maximum concentration. In contrast, the curve for the cerebellum was shallow and exhibited a smaller maximal response (approximately 60%). Apparent affinity for muscimol also differed among these brain regions. The regional differences in 36Cl- uptake induced by THDOC and pentobarbital were not as apparent as those induced by muscimol; however, the maximal modulatory effect of pentobarbital in the hippocampus was significantly higher than that in the cerebellum. In rats treated subacutely with a subconvulsive dose of bicuculline, a significant increase in muscimol-stimulated 36Cl- uptake was observed in the cerebellum but not in the frontal cortex or hippocampus. Analysis of the concentration-response curves for muscimol-stimulated 36Cl- uptake in the cerebellum revealed that the Vmax for muscimol in the subacutely treated group was significantly higher than those for muscimol in the control and acutely treated groups without any differences in the KD value.(ABSTRACT TRUNCATED AT 250 WORDS)

Confirmation of the anxiolytic-like effect of dihydrohonokiol following behavioural and biochemical assessments

“…Cl N uptake into cortical synaptoneurosomes Cortical synaptoneurosomes were prepared in the same way as previously reported (Hollingsworth et al 1985 ;Suzudak et al 1986 ;Ito et al 1992Ito et al , 1995Ito et al , 1996. Briefly, mouse cerebral cortices were homogenized in 5 volumes of ice-cold Krebs-Henseleit buffer (pH 7.4) using a glass-glass homogenizer.…”

Meldrum’s acid and related compounds in the synthesis of natural products and analogs

“…168 Muscimol is a potent selective agonist for one of the brain's primary neurotransmitters GABA A . 169 Ibotenic acid, structurally similar to glutamate, interacts non-selectively with all types of (S)-glutamate receptors. 170 Despite the importance of the 3-hydroxyisoxazole pharmacophore for biomedical research, the existing routes to 3hydroxyisoxazoles normally required multi-step and lowyielding sequences.…”

Dihydromagnolol – a Potent Anxiolytic-like Agent in Mice

“…The effect of DHM on 36 Cl -uptake into mouse cortical synaptoneurosomes was evaluated according to the method described elsewhere (Ito et al, 1992(Ito et al, , 1995(Ito et al, , 1996. Briefly, mouse cerebral cortices were homogenized in 5 vol of icecold Krebs-Henseleit buffer (pH 7.4).…”